Slip Flow Chromatography

滑流色谱

• 批准号: 8913219
• 负责人: MARY J. WIRTH
• 金额: $ 50.1万
• 依托单位: BIOVIDRIA, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8913219
• 关键词: Accounting; Adopted; Adverse drug effect; Antibodies; Autoimmune Diseases; Biomedical Engineering; Blood capillaries; Caliber; Chromatography; Collaborations; Column Chromatography; Crystal Formation; Development; Diagnostic; Diffusion; Disulfides; Drug Formulations; Drug Industry; Goals; Health; Height; Heterogeneity; Humidity; IgG1; IgG2; IgG4; Immunoglobulin G; Length; Malignant Neoplasms; Manufacturer Name; Marketing; Measurement; Methods; Molecular; Monitor; Monoclonal Antibodies; Patients; Peptides; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Preparation; Procedures; Process; Protein Isoforms; Proteins; Reagent; Relative (related person); Reproducibility; Research; Resolution; Sampling; Silanes; Silicon Dioxide; Small Business Technology Transfer Research; Specificity; Stainless Steel; Toxic effect; Universities; Water; Width; base; capillary; commercialization; design; immunogenicity; innovation; instrument; new technology; particle; polymerization; reversed phase chromatography; scale up; self assembly; silane; silanol; tumor

DESCRIPTION (provided by applicant): The goal of this STTR Phase II collaboration between Purdue University and bioVidria, Inc. is to commercialize disruptive new technology for protein chromatography and then maximize its impact by serving the fastest growing segment of the pharmaceutical industry: protein drugs. The product is a reversed phase chromatography column that uses silica particles of only 500 nm in diameter, thereby significantly increasing resolution and sensitivity in protein separations. Slip flow is what enables high flow rates with such small particles. The primary market opportunity is the analysis of the heterogeneity of bioengineered drugs based on monoclonal antibodies. These drugs offer high target specificity, e.g., toxicity directed at the tumor. The problem to be solved is that monoclonal antibodies can undergo intra- and inter-molecular disulfide scrambling during storage, which causes immunogenicity in patients. The proposed slip-flow column will uniquely resolve and isolate these scrambled versions, enabling rational design of formulations to reduce immunogenicity. The Phase I research focused on protein and peptide separations in packed capillaries, demonstrating ten-fold narrower zones and a ten-fold flow enhancement from slip flow. The Phase II research will focus on scaling up to develop packed stainless steel columns of 2.1 mm in diameter. The scale-up will allow customers to use these columns with current commercial instruments, which is essential for serving the pharmaceutical industry. The Specific Aims of the Phase II proposal are to 1) optimize the process for packing 500 nm particles into stainless steel columns, 2) develop a scalable process to make bonded phases with negligible silanol activity, and 3) develop separation methods for resolving products of disulfide rearrangement of monoclonal antibodies for all three types of antibody platforms. We enlist three major companies to provide samples: Genentech (IgG1), Pfizer (IgG2) and Eli Lilly (IgG4).

描述（由申请人提供）：普渡大学和Biovidria，Inc。之间的这一STTR II期合作的目标是使蛋白质色谱的破坏性新技术商业化，然后通过服务于制药行业增长最快的细分市场来最大程度地影响其影响：蛋白质药物。该产物是相反的相色谱柱，它使用直径仅为500 nm的二氧化硅颗粒，从而显着提高了蛋白质分离的分辨率和敏感性。滑动流量是如此小的颗粒使高流速。主要市场机会是分析基于单克隆抗体的生物工程药物的异质性。这些药物具有较高的靶标特异性，例如针对肿瘤的毒性。要解决的问题在于，单克隆抗体可以在储存过程中发生二硫键和分子间二硫化物，这会导致患者的免疫原性。 拟议的滑动柱将唯一解决并隔离这些炒版，从而使制剂的理性设计能够降低免疫原性。第一阶段的研究集中在填充毛细血管中的蛋白质和肽分离上，表明较窄的区域和滑动流量的增强了十倍的流量。 II期研究将着重于扩大直径为2.1 mm的不锈钢柱。扩大规模将使客户可以将这些列与当前的商业仪器一起使用，这对于为制药行业提供服务至关重要。第二阶段提案的具体目的是：1）优化将500 nm颗粒包装到不锈钢柱中的过程，2）开发一个可扩展的过程，以使粘合的相位具有可忽略的硅烷醇活性，而3）开发分离方法，用于解决三种类型的单核抗体的二硫化物二硫化物重排的产物，以解决三种类型的antibsody antibsody的单位抗体。我们邀请三家主要公司提供样品：Genentech（IgG1），辉瑞（IgG2）和Eli Lilly（IGG4）。